Combination therapy for preventing or treating alzheimer's disease, and kit therefor

Abstract

The invention relates to a method for preventing or treating Alzheimer's disease (AE). According to said method, a means for inducing a sequestration of amyloid β (Aβ) into a plasma is administered to a person, and the person is treated by means of an apheresis device comprising a fixed carrier that can come into contact with the blood or plasma flow and comprises a receptor binding an amyloid-β-precurser-protein (APP), the APP being removed from the blood of the person by means of the apheresis device. The invention also relates to a set for carrying out said method.

1 . A kit for preventing or treating Alzheimer's Disease (AD), comprising
 an agent for inducing a sequestration of amyloid β (Aβ) in plasma, and   an apheresis device that comprises a solid carrier which can be brought into contact with the blood or with the plasma flux, which carrier has a receptor that binds the amyloid-β-precursor protein (APP).   
     
     
         2 . The kit according to  claim 1 , characterized in that the APP-binding receptor is selected from anti-APP antibodies, Aβ-binding receptors, in particular anti-Aβ40 antibodies or anti-Aβ42 antibodies, APP-binding proteins, in particular gelsolin, apoJ or apoE, APP-binding peptides, APP binding glycolipids, preferably gangliosides, in particular GM1, or APP-binding nucleic acids, in particular aptamers, or mixtures of said receptors. 
     
     
         3 . The kit according to  claim 1  or  2 , characterized in that the carrier is a sterile and pyrogen-free column. 
     
     
         4 . The kit according to any one of  claims 1  to  3 , characterized in that the agent for inducing a sequestration of amyloid β (Aβ) in plasma is selected from agents with a high affinity to Aβ, in particular gelsolin or GM1, Aβ-specific antibodies, peptides or nucleic acids, or a Aβ-specific active or passive vaccine. 
     
     
         5 . The kit according to any one of  claims 1  to  4 , characterized in that the Aβ-specific active vaccine is an Aβ-derivative or an Aβ-mimotope. 
     
     
         6 . The kit according to  claim 5 , characterized in that the Aβ-derivative is selected from peptides which partially or fully consist of D amino acids and/or non-natural amino acids. 
     
     
         7 . The kit according to  claim 5 , characterized in that the Aβ-mimotope consists of a peptide or comprises a peptide of formula
   X1X2X3X4X5X6, 
 wherein X1 is an amino acid, C excepted, 
 X2 is an amino acid, except C, 
 X3 is an amino acid, except C, 
 X4 is an amino acid, except C, 
 X5 is an amino acid, except C, 
 X6 is an amino acid, except C, 
 and wherein X1X2X3X4X5X6 is not DAEFRH, the peptide having a binding capacity to an antibody which is specific for the natural N-terminal Aβ42 sequence DAEFRH, and 5-mers thereof having a binding capacity for the antibody being specific for the natural N-terminal Aβ42 sequence DAEFRH. 
 
     
     
         8 . The kit according to  claim 7 , characterized in that in the formula X1X2X3X4X5X6 there:
 X1 is G or an amino acid with a hydroxyl group or a negatively charged amino acid, preferably E, Y, S or D,   X2 is a hydrophobic amino acid or a positively charged amino acid, preferably I, L, V, K, W, R, Y, F or A,   X3 is a negatively charged amino acid, preferably D or E,   X4 is an aromatic amino acid or L, preferably Y, F or L,   X5 is H, K, Y, F or R, preferably H, F or R, and   X6 is S, T, N, Q, D, E, R, I, K, Y or G, preferably T, N, D, R, I or G,   in particular EIDYHR, ELDYHR, EVDYHR, DIDYHR, DLDYHR, DVDYHR, DIDYRR, DLDYRR, DVDYRR, DKELRI, DWELRI, YREFFI, YREFRI, YAEFRG, EAEFRG, DYEFRG, ELEFRG, DRELRI, DKELKI, DRELKI, GREFRN, EYEFRG, DWEFRDA, SWEFRT, DKELR, DAEFRWP, DNEFRSP, SAEFRTQ, SAEFRAT, SWEFRNP, SWEFRLY, SWELRQA, SVEFRYH, SYEFRHH, SQEFRTP, SSEFRVS, DWEFRD, DAELRY, DWEL RQ, SLEFRF, GPEFRW, GKEFRT or SFEFRG.   
     
     
         9 . A method for preventing or treating Alzheimer's Disease (AD), wherein
 an agent for inducing a sequestration of amyloid β (Aβ) into plasma is administered to a person and the person is treated with an apheresis device that comprises a solid carrier which can be brought into contact with the blood or the plasma flux, said carrier having an amyloid-β-precursor-protein(APP)-binding receptor, wherein APP is removed from the blood of the person by means of the apheresis device.   
     
     
         10 . The method according to  claim 9 , wherein a kit according to any one of  claims 1  to  8  is used. 
     
     
         11 . Use of an Aβ-mimotope, as defined in  claim 7  or  8 , for producing an agent which is to be used in a combination therapy, as defined in  claim 1 , for preventing or treating AD.